Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673720 | SCV000798955 | likely pathogenic | Alstrom syndrome | 2018-03-29 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673720 | SCV002819296 | likely pathogenic | Alstrom syndrome | 2022-12-06 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.4344dupT/p.Glu1449X (also known as c.4350dupT/p.Glu1451X in RefSeq) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249282 control chromosomes. To our knowledge, no occurrence of c.4344dupT in individuals affected with Alstrom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Invitae | RCV000673720 | SCV004276269 | pathogenic | Alstrom syndrome | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1451*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs778728424, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 557563). For these reasons, this variant has been classified as Pathogenic. |